The regulation of thyroid growth is only partially defined. Traditionally, thyroid stimulating hormone (TSH) has been viewed as the hormone controlling thyroid cell proliferation and differentiation. For this reason, current therapy for thyroid goiter and nodules, a prevalent endocrine disorder, is directed at TSH suppression. However, factors other than TSH may play an important role in regulating normal and abnormal thyroid growth. In vitro TSH is not a growth factor for several species of thyroid growth frequently occurs elevations in circulating TSH concentrations. Other physiologically occurring growth factors have recently been shown to affect thyroid growth and differentiation. Included among these are the insulin-like growth factors (IGFs), a family of polypeptides which appear to act in an autocrine or paracrine manner to modulate tissue function locally. The aim of the proposed research would be to examine the role of IGFS in modulating thyroid growth and differentiation. Increased understanding of the physiology and pathophysiology of thyroid growth may contribute to improved management of thyroid masses. Both in vitro and in vivo experimental models will be used to study IGF action, receptors, and production in the thyroid. The effects of the IGFs on cell division, iodine metabolism, and glucose and amino acid uptake will be assessed in ovine thyroid cells, a well- established, serum-free tissue culture system. These cells will also be used to characterize thyroid IGF receptors and the media factors potentially regulating their abundance or affinity. In vitro production of IGFs will be determined by measuring IGFs in media conditioned by these cells as well as the content of messenger RNA (mRNA) encoding for IGFs within the cells. Production of IGF carrier protein will also be examined since these have been shown to influence the biologic activity of the IGFs. We will also assess the role of IGFs in normal and abnormal thyroid growth in vivo. Tissues from normal and experimentally-induced rats as well as human pathological thyroid specimens will be used to quantitate IGF binding, peptide concentration, and mRNA.